The TESTING Study: Steroids vs. Placebo in High Risk IgA Nephropathy
Bibliographic record
Abstract
Background: The Therapeutic Evaluation of STeroids in IgA Nephropathy Global (TESTING) study assessed the effects of oral methylprednisolone compared to placebo on major kidney outcomes and safety in IgAN. Methods: This investigator-initiated, double-blind randomized trial included people with IgAN, proteinuria ≥1g/day and eGFR 20-120 mL/min/1.73m2, following ≥3 months of optimized background care including RAS blockade. Participants were randomized 1:1 to methylprednisolone (0.6-0.8 mg/kg/day, maximum 48 mg/day, for 2 months then weaning by 8mg/day/month) or to matching placebo. In 2016, due to an excess of serious infections in the steroid arm, the methylprednisolone dose was reduced (0.4 mg/kg/day, maximum 32 mg/day, weaning by 4 mg/day/month) and pneumocystis jirovecii prophylaxis added. The primary endpoint was the composite of 40% eGFR decline or kidney failure (dialysis, transplantation or death due to kidney disease) with prespecified secondary and safety outcomes. Results: In total, 503 participants (mean age 38 years, 39% female, mean eGFR 61.5 mL/min/1.73m2, proteinuria 2.46 g/day) were randomised to methylprednisolone (257) or placebo (246), including 262 to the full dose and 241 to the reduced dose protocols. Over 4.2 years average follow up, methylprednisolone reduced the risk of the primary outcome by 47% (event rate 7.0 vs 11.8/100 patient years, HR 0.53, 95% CI 0.39-0.72, p <0.0001), and ESKD by 41% (HR 0.59, CI 0.40-0.87, p=0.008). The reduction in risk was seen across both dose protocols (p heterogeneity 0.11): full dose HR 0.58 (95% CI 0.41-0.81), reduced dose HR 0.27 (95% CI 0.11-0.65). Serious adverse events were more frequent with steroids compared to placebo (28 vs 7 patients, p=0.0004), particularly with the full dose (22 vs 4, p=0.0003) vs the reduced dose regimen (6 vs 3, p=0.50). Conclusions: Steroids reduce the risk of major kidney outcomes and kidney failure in people with high risk IgAN. The incidence of serious adverse events is increased mainly with high dose therapy. *joint first (JL MW)/senior authors (HZ VP) Funding: Government Support - Non-U.S.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.003 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.004 | 0.003 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.010 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".